Composition for controlling coccidiosis



Patented Nov. 28, 1950 COMPOSITION FOR CONTROLLING 'COCCIDIOSIS Emanuel Waletzky, Stamford, Conn, assignor to American Cyanamid Company,

New York,

N. Y., a corporation of Maine No Drawing. Application December so, 1948, Serial No. 68,400

7 Claims. 1

This invention deals with measures for the mitigation and control of coccidiosis and more particularly with means for the administration of these measures.

Coccidiosis is a protozoan disease that affects the intestinal tract. The disease is prevalent in poultry, sheep, and calves and has its greatest effect on immature birds and mammals. It has been estimated that 12 to 20% of all chicks hatched in the United States die from cecal coccidiosis before they reach the age of one month. While not as lethal to mammals, weight loss and downgrading of the mammalian livestock, due to coccidial infection and consequent debilitation, amounts to economic losses measured in the millions of dollars annually.

It has been discovered that certain meta-nitrobenzenesulfonamides possess a specific anticoccidial efiect. These compounds are distinguished by the formula wherein R1 and R2 can be the same or different and represent hydrogen, halogen, and alkyl radicals. The hydrogen atoms on the amide nitrogen are acidic in character and may be replaced with a cationic salt-forming radical by simple neutralization with a base or by double decomposition. Such compounds are also active and are included within the scope of the invention. When R1 and/or R2 are alkyl the total carbon atom content of R1 and R2 may be up to about eight carbon atoms. At higher carbon contents the eniciency of the compounds falls off rapidly.

These compounds administered preferably by way of a medicated feed to the extent of 5 to 250 milligrams per kilogram of animal weight per day, the precise dosage depending on the particular compound and the severity of their infection prevent losses from coccidiosis if administration is started within three days of ingestion of the infective oocysts. These compounds, when administered at the requisite concentration show little or no toxic effects. The nutrition, rate of growth, and general well-being are not disturbed.

Concentrations of these compounds within the above range of administration while halting the severe ravages and often fatal consequences of the disease, permit mild infections, which enable the host to develop an active immunity against the infection. This immunity does protect the animal or fowl after the discontinuation of the medicated feed, even on heavily contaminated premises.

Test animals, which have ingested infected oocysts in amounts which kill more than of the controls, recover and flourish if these compounds are administered up to 72 hours after infection. When the treatment has been delayed, administration should be in the range of the higher concentrations and should continue at these concentrations for at least two days. However, these compounds can be most effectively administered as prophylactic long-term continuous treatments at low concentrations in the feed.

The compounds of this invention were evaluated by comparing them with sulfaguanidine, which, to date has been one of the most effective and safest medications for the control of coccidiosis. The results show they are manyfold as effective as sulfaguanidine, and are completely safe for routine treatment, since they possess sufficient margin between therapeutic dosage and dosages which affect only slightly the rate of gain in weight of healthy animals.

The specificity of the compounds which are the subject of this invention will be apparent from a consideration of the table and discussion which follows.

Some of the compounds of the present invention which we have found effective and their approximate efiectiveness as compared to sulfaguanidine are shown in the following table. The compounds were administered in various concentrations in the test ration and the sulfaguanidine ratio was established by determining the minimum amount of the test compound which affords the same protection to the test animals as does the established dosage of sulfaguanidine and dividing the latter by the former. In other words, a sulfaguanidine ratio of 20 indicates that .05 gm. of the test compound affords the same protection to the animal as would 1.00 gm. of sulfaguanidine.

3 Table Sulfaguani- Name dine Ratio m-nitroben yen e nl frm amide N-methyl-m-nitrobcnzencsu1f onamide N,Ndimethy1-m-nitrobenzenesulionamide N -etl1yl-m-nitrobenzenesulfonamidc N-chloro-N-ethyl-m-nitrobenzenesulfonamide N,N-diethyl-m-nitrobenzenesullonamide. Nn-propyl-m-nltrobenzcnesullonamidc ,N-di-n-prpyl-mnitrob enzenesullona -i o-proply-m-nitrobenzcnesulfonamide.l ,N-(liisopropyl'm-nitrobcnzcncsulfonamide. a (n-butyl) -m-nitrobenzenesulfonamide -isoamyl-m-nitrobenzenesulfonamide N -n-Octyl-m-nitrobenzcnesulionamide Potassium N -chloro-m-nitrobenzenesullona N ,N-dichloro-m-nitrobenzcnesulfonamide N,N-dibromo-m-nitrobcnzenesulfonamide N -chloro-N -ethylm-nitrobeuzenesulfonamide In contrast to the compounds of this invention,

many closely related compounds areeither have tive or toxic or both. For example, N acetyl-nj nitrobenzenesulfonamide and N -propionyl-m-ni trobenzenesulfonamide are both severelytoigic at one-fifth the sulfaguanidine dosage. N-benzoylm-nitrobenzenesulfonamide and lil-phenylbenzenesiilfonamide areboth completely inactive; at twicethefsulfa guarii dos'a'gei N-m'emy -N- nitro' m 'nitrobenzenesulfonami'de and 'N-cyclohexyl m nitrobenz enesulfonamide are inactive even at three ftimes jth'ef sulfaguanidine dosage.

3,55dinitrobenzenesulfonamide "is 'inactive at five times the"sulfaguanidinejdosagewhile 5-nitro-iotoluenesulfon'amide i'stoizic at one seventh of the M-bromobenzenenormal sulfaguanidine dose. sulfonamidefa'ndi p-iiitrobenzenesulfonamide" are bothtoxicQtheformer at Lone-eighth and the latter? at one-fifth" of the normal 7 sulfagu'anidine dosage, 'Fromtheabove it'can'be seen that the locationof the nitrogroup atthe' meta position on" thdbenzene ring is necessary for the anticoccidial effect. A 'great many compounds closely related to those of this inventionfin addition to sementioned abovefhavebeen tested, bu't were m toxic; ineliective' or both.

Althoughthe birds br'animals may be given direct individual doses ofthese compounds'by oraljadmini stration one ormore'ftimesa day, the

which a compound of' thejinvention is 7 mixed. Suchimedicate'd feeds should contain enoughof the drug so that the dosage range indicated above daily diet,

"The preferred mannerof supplying the compounds ofthe present 'intentionfor administra'-' tion' is to thoroughly mix theanti-co'ccidial agent willbe ingested by animals in; their "normal i in the animals feedin the concentration ranges The higher concentration indicated *bemw. ranges may be mixedwith all or selected portions of 'tlie animals daily rations, the concentration being so regulated that "the animal will ingest 'gms. of the'drugper kilogram of daily 5 to 250m body weight.

In the 'case of chickens or other fowl, such medicated feed should contain from about .005.

to 0.2% of these compounds in'thefood when the treatment is Me long term nature, to protect the birds from the deleterious consequences of acute infection over longperiods of time. Of course, if

whel'en Ri and R2 are chosen from the group consisti ng of hydrogen, cationic radicals, halogens,

and allgyl radicals of less than nine carbon atoms in the concentration of at least 0.005% by weight.

A'Q WPQ iF QQ qfl-m terefie tive a ro in qeid esis. 9 r si e mula where R1 and R2 arechosen from the group consistiiig of hydrogenfeationic 'radic'als', halogens, and alkyl radicals of less than nine carbon atoms;

'3. A'inedicated'poultry "aha animal'fed ell-cc tive n on l in ,r sei s s, ntain m anitrobenzenesulfonamide, and an edible" carrier. 4. A medicated poultry andanimal feed efiec tive' in controlling coccidiosis; containing a metanitrosulfonamidohalide, and an edible carriei'l 5. An anticoccidial agent comprising animal feed and N,N-dichloro-m-nitrobenzenesulfonamide. i

6. A medicated poultry and animal feed efiective in controlling coceidiosis, containing an alkyl meta-nitrobenzenesulfonamide wherein the alkyl radical is less than nine carbon atoms and an edible carrier. 4

7 antieoccidial agent comprising animal d i ee aeth lmehiea ne su amide.

' M N E WAP TZKK1 CITED ellt NITED"SE TESH AT E Number Name Date 2279321 i i al i P PP: 1 9 .2

QTHEB Rosenthal Public Health Reports vol. 58,- pages 5 toQlJa'n (Copy in Scientific Library.)

e refe en are eQ0rg n.the, 

1. A MEDICATED POULTRY AND ANIMAL FEED EFFECTIVE IN CONTROLLING COCCIDIOSIS, CONTAINING AN EDIBLE SUBSTANCE AND COMPOUNDS OF THE GENERAL FORMULA 